BACKGROUND: We assessed whether treatment interruptions induce selection of mutations associated with drug resistance in the Swiss-Spanish Intermittent Treatment Trial (SSITT). Patients had been on HAART without previous failure and had undetectable viraemia for at least 6 months. Their HAART was interrupted for 2 weeks and restarted for 8 weeks. After four of these cycles, treatment was definitively interrupted at week 40. METHODS: Genotypic resistance testing was performed in 87/97 Swiss patients: in those failing treatment before week 40, at the time of first viral rebound > 500 copies/ml off treatment and preceding failure to reach RNA < 50 copies/ml after 8 weeks of re-treatment; for patients without virological failure, on the first sample with HIV-1 RNA > 1000 copies/ml after week 40. RESULTS: Mutations associated with drug resistance were detected in 9/25 (36%) patients with virological failure during the first 40 weeks and in 6/59 (10%) patients after week 40. Overall, drug resistance mutations were detected in 17% of patients, all but two with the 184V/I mutation. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. A wild-type codon at position 184 was detected in previous samples in all but two. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007). CONCLUSIONS: The M184V/I mutation is frequently selected during repeated treatment interruptions.
BACKGROUND: We assessed whether treatment interruptions induce selection of mutations associated with drug resistance in the Swiss-Spanish Intermittent Treatment Trial (SSITT). Patients had been on HAART without previous failure and had undetectable viraemia for at least 6 months. Their HAART was interrupted for 2 weeks and restarted for 8 weeks. After four of these cycles, treatment was definitively interrupted at week 40. METHODS: Genotypic resistance testing was performed in 87/97 Swiss patients: in those failing treatment before week 40, at the time of first viral rebound > 500 copies/ml off treatment and preceding failure to reach RNA < 50 copies/ml after 8 weeks of re-treatment; for patients without virological failure, on the first sample with HIV-1 RNA > 1000 copies/ml after week 40. RESULTS: Mutations associated with drug resistance were detected in 9/25 (36%) patients with virological failure during the first 40 weeks and in 6/59 (10%) patients after week 40. Overall, drug resistance mutations were detected in 17% of patients, all but two with the 184V/I mutation. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. A wild-type codon at position 184 was detected in previous samples in all but two. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007). CONCLUSIONS: The M184V/I mutation is frequently selected during repeated treatment interruptions.
Authors: Ari Bitnun; Lindy Samson; Tae-Wook Chun; Fatima Kakkar; Jason Brophy; Danielle Murray; Shawn Justement; Hugo Soudeyns; Mario Ostrowski; Shariq Mujib; P Richard Harrigan; John Kim; Paul Sandstrom; Stanley E Read Journal: Clin Infect Dis Date: 2014-06-09 Impact factor: 9.079
Authors: Emmanouil Papasavvas; Jay R Kostman; Karam Mounzer; Robert M Grant; Robert Gross; Cele Gallo; Livio Azzoni; Andrea Foulkes; Brian Thiel; Maxwell Pistilli; Agnieszka Mackiewicz; Jane Shull; Luis J Montaner Journal: PLoS Med Date: 2004-12-28 Impact factor: 11.069
Authors: Beda Joos; Alexandra Trkola; Marek Fischer; Herbert Kuster; Peter Rusert; Christine Leemann; Jürg Böni; Annette Oxenius; David A Price; Rodney E Phillips; Joseph K Wong; Bernard Hirschel; Rainer Weber; Huldrych F Günthard Journal: J Virol Date: 2005-07 Impact factor: 5.103